| First Author | Zhang B | Year | 2014 |
| Journal | J Immunol | Volume | 192 |
| Issue | 3 | Pages | 1055-1063 |
| PubMed ID | 24379125 | Mgi Jnum | J:207300 |
| Mgi Id | MGI:5555983 | Doi | 10.4049/jimmunol.1302694 |
| Citation | Zhang B, et al. (2014) Id3 and Id2 act as a dual safety mechanism in regulating the development and population size of innate-like gammadelta T cells. J Immunol 192(3):1055-63 |
| abstractText | The innate-like T cells expressing Vgamma1.1 and Vdelta6.3 represent a unique T cell lineage sharing features with both the gammadelta T and the invariant NKT cells. The population size of Vgamma1.1(+)Vdelta6.3(+) T cells is tightly controlled and usually contributes to a very small proportion of thymic output, but the underlying mechanism remains enigmatic. Deletion of Id3, an inhibitor of E protein transcription factors, can induce an expansion of the Vgamma1.1(+)Vdelta6.3(+) T cell population. This phenotype is much stronger on the C57BL/6 background than on the 129/sv background. Using quantitative trait linkage analysis, we identified Id2, a homolog of Id3, to be the major modifier of Id3 in limiting Vgamma1.1(+)Vdelta6.3(+) T cell expansion. The Vgamma1.1(+)Vdelta6.3(+) phenotype is attributed to an intrinsic weakness of Id2 transcription from Id2 C57BL/6 allele, leading to an overall reduced dosage of Id proteins. However, complete removal of both Id2 and Id3 genes in developing T cells suppressed the expansion of Vgamma1.1(+)Vdelta6.3(+) T cells because of decreased proliferation and increased cell death. We showed that conditional knockout of Id2 alone is sufficient to promote a moderate expansion of gammadelta T cells. These regulatory effects of Id2 and Id3 on Vgamma1.1(+)Vdelta6.3(+) T cells are mediated by titration of E protein activity, because removing one or more copies of E protein genes can restore Vgamma1.1(+)Vdelta6.3(+) T cell expansion in Id2 and Id3 double conditional knockout mice. Our data indicated that Id2 and Id3 collaboratively control survival and expansion of the gammadelta lineage through modulating a proper threshold of E proteins. |
